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The Rapidity of Drug Dose Escalation Influences Blood Pressure Response and Adverse Effects Burden in Patients With Hypertension
The Quinapril Titration Interval Management Evaluation (ATIME) Study
John M. Flack, MD, MPH;
Carla Yunis, MD, MPH;
John Preisser, PhD;
Charles B. Holmes, MD, MPH;
George Mensah, MD;
Barry McLean, MD;
Elijah Saunders, MD;
for the ATIME Research Group
Arch Intern Med. 2000;160:1842-1847.
Background Antihypertensive medication doses are typically increased within several weeks after initiation of therapy because of inadequate blood pressure (BP) control and/or adverse effects.
Methods We conducted a parallel-group clinical trial with 2935 subjects (53% women, n=1547) aged 21 to 75 years, with Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI stages 1 to 2 hypertension, recruited from 365 physician practices in the southeastern United States. Participants were randomized either to a fast (every 2 weeks; n=1727) or slow (every 6 weeks; n=1208) drug titration. Therapy with quinapril, an angiotensin-converting enzyme inhibitor, was initiated at 20 mg once daily. The dose was doubled at the next 2 clinic visits until the BP was lower than 140/90 mm Hg or a dose of 80 mg was reached.
Results Pretreatment BP averaged 152/95 mm Hg. Patients with stage 2 hypertension reported more symptoms than those with stage 1. The BP averaged 140/86, 137/84, and 134/83 mm Hg in the slow group compared with 141/88, 137/85, and 135/84 mm Hg in the fastgroup at the 3 respective clinic visits. The BP control rates to lower than 140/90 mm Hg at the 3 clinic visits were (slow, fast, respectively) 41.3%, 35.7% (P<.001); 54.3%, 51.5% (P=.16); and 68%, 62.3% (P=.02). In the fast group, 10.7% of participants experienced adverse events vs 10.8% in the slow group; however, 21.0% of adverse events in the fast group were "serious" vs only 12% in the slow group.
Conclusion Slower dose escalation of the angiotensin-converting enzyme inhibitor quinapril provides higher BP control rates and fewer serious adverse events than more rapid drug dose escalation.
From the Department of Internal Medicine, Cardiovascular Epidemiology and Clinical Applications Program, Division of Endocrinology, Metabolism, and Hypertension, and the Department of Community Medicine, Wayne State University Medical School, the Detroit Medical Center, and the John D. Dingell Veterans Administration Medical Center, Detroit, Mich (Dr Flack); the Department of Surgical Sciences, Hypertension and Vascular Medicine Center (Dr Yunis), and the Department of Public Health Sciences, Wake Forest University School of Medicine (Drs Yunis and Preisser), Winston-Salem, NC; the Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (Dr Holmes); the Department of Cardiology, Augusta Veterans Administration Medical Center, Augusta, Ga (Dr Mensah); the Department of Internal Medicine, High Blood Pressure Center, Professional Office Building, Birmingham, Ala (Dr McLean); and the Division of Hypertension, University of Maryland School of Medicine, Baltimore (Dr Saunders). A list of the members of the ATIME Research Group is available from Carla Yunis, MD, Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157.
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